Developing electropositive citric acid–polyethylenimine carbon quantum dots with high biocompatibility and labeling performance for mesenchymal stem cells in vitro and in vivo

Abstract

Although mesenchymal stem cells (MSCs) have been widely adopted to cure many types of diseases, how they migrate to damaged tissues is still not clear. Thus, it is significant to develop imaging materials for clarifying the migration and distribution of MSCs in vivo. Herein, positively-charged carbon quantum dots (CA–PEI CQDs) were synthesized for the first time via a hydrothermal method by adopting a certain ratio of citric acid (CA) to polyethylenimine (PEI). The surface of the CA–PEI CQDs is positive (0.5 mV), and they have an average size of around 4.58 nm. The CA–PEI CQDs exhibit their strongest emission peak at 440 nm at an excitation wavelength of 320 nm, where the corresponding quantum yield is 9.97% and the fluorescence lifetime is 1.7 ns. Cellular toxicity testing supports that the CA–PEI CQDs exhibit the highest reported biocompatibility for human MSCs and blood cells (800 μg mL⁻¹). Furthermore, CA–PEI CQDs not only image MSCs markedly in vitro, located in the cytoplasms of MSCs, but can also be used to track the migration of MSCs in lupus MRL/lpr mice. This is the first report of CQDs with such high biocompatibility (800 μg mL⁻¹) for MSCs and their application in tracing the migration of MSCs in vivo. This study is helpful for further dissecting the molecular mechanism underlying MSC therapy to alleviate diseases.